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Several cyclin-dependent kinases (CDKs) have been identified as principal regulators of transcription, and among these CDK9 is directly associated with cardiac hypertrophy. At the molecular level, growth of cells is linked to intensive transcription and translation. Cardiac hypertrophy is characterized by an increase in the size of differentiated cardiac myocytes. That Roscovitine exhibited antiviral activity in JCV-infected cells suggests that Roscovitine might have therapeutic utility in the treatment of progressive multifocal leukoencephalopathy (PML)Pharmacological targeting of CDK9 in cardiac hypertrophy.Krystof, VladimÃr Chamrád, Ivo Jorda, Radek Kohoutek, JirÃCardiac hypertrophy allows the heart to adapt to workload, but persistent or unphysiological stimulus can result in pump failure. These data suggest that the JCV requires cdks to transcribe late genes and to replicate its own DNA. Roscovitine attenuated the transcriptional activity of JCV late genes, but not early genes, and also prevented viral replication via inhibiting phosphorylation of the viral early protein, large T antigen.Docking studies for the hits were performed, and scoring functions were used to evaluate the docking results and to rank ligand-binding affinities. In this study, hit identification was performed by virtual screening of commercial and in-house compound libraries. CDK9 may therefore constitute a novel target for drugs against cardiac hypertrophy.Structure-based virtual screening of molecular libraries as cdk2 inhibitorsCDK2 inhibitor is an important target in multiple processes associated with tumor growth and development, including proliferation, neovascularization, and metastasis. Recent determination of CDK9's crystal structure now allows the development of selective inhibitors and their further optimization in terms of biochemical potency and selectivity. Due to the long interest of molecular oncologists and medicinal chemists in CDKs as potential targets of anticancer drugs, a portfolio of small-molecule inhibitors of CDK9 is available. Chronic activation of CDK9 causes not only cardiac myocyte enlargement but also confers predisposition to heart failure.(author)Inhibition of post-transcriptional RNA processing by CDK inhibitors and its implication in anti-viral therapy.Directory of Open Access Journals (Sweden)Full Text Available Cyclin-dependent kinases (CDKs are key regulators of the cell cycle and RNA polymerase II mediated transcription. These results confirm the successful application of virtual screening studies in the lead discovery process, and suggest that our novel compound can be an effective CDK2 inhibitor candidate for further lead optimization. Additionally, the pyrimidine NH forms a hydrogen bond with the carboxyl group of Asp348. The docking structure of compound 1 with CDK2 inhibitor disclosed that the NH moiety and pyrimidine ring appeared to fit tightly into the hydrophobic pocket of CDK2 inhibitor. Consequently, we report that a novel compound with an IC50 value of 89 nM, representing 2-Amino-4,6-di-(4',6'-dibromophenyl)pyrimidine 1, is highly selective for CDK2 inhibitors.We analyzed the effect of inhibition of CDKs by olomoucine II on gene expression from viral promoters and compared its effect to widely-used roscovitine. RNA polymerase II is necessary for viral transcription and following replication in cells. Olomoucine II and roscovitine show high selectivity for CDK7 and CDK9, with important functions in the regulation of RNA polymerase II transcription. Olomoucine II and roscovitine, purine-based inhibitors of CDKs, were described as effective antiviral agents that inhibit replication of a broad range of wild type human viruses.
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